Glaucoma is a leading cause of blindness and visual morbidity. Because the disease causes irreversible damage to neural tissue it is of upmost importance to identify glaucoma and its progression at the earliest possible stages. Through advancements in the use of optical coherence tomography (OCT) and other technologies, the long-term goal of this research project is to precisely and accurately detect ocular structural and functional changes associated with glaucoma and to identify eyes with glaucoma that are at risk for future disease progression. This is accomplished by consolidating our long-term data acquired from various generations of OCT technology over the last 19 years. By using innovative methods for image quality improvement along with signal morphing, it is now possible to reliably bridge data acquired by the different generations and manufacturers of OCT, creating the longest-term cohort of longitudinal OCT measurements of the retina and optic nerve head regions. Advanced retinal segmentation software will be applied enabling detailed discrimination of all retinal layers even in the presence of ocular co-morbidity coincident with glaucoma (a previous exclusion criteria), allowing maximal use of subject and patient data. Using this cohort, two methods will be uniquely applied for determining the long-term relationship between structure and function: Continuous-time hidden Markov model and Latent differential equation models. This would enhance understanding of the disease process and allow determination of the best methods to identify disease and its progression at various stages. We will utilize advanced innovative imaging technologies and methods to accurately and precisely detect evidence of early structural changes: Swept-source OCT, Adaptive-optics OCT and Polarization-sensitive OCT. These technologies will be used to image the retina, sclera and optic nerve head providing enhanced information of the lamina cribrosa and birefringence properties. Scans will be also acquired during and following provocative acute IOP elevation testing to asses the morphological and biomechanical responses as potential markers for current and future disease characterization. The outcomes of this research project will provide an innovative and enhanced evaluation of ocular structure and function in glaucoma that will expand our understanding of the disease pathophysiology, offer new diagnostic tools for early disease detection and disease progression and identify subjects at risk for rapid glaucoma progression.